Phenotypes Associated with This Genotype

Genotype
MGI:4943534

• Allelic Composition: Pten^tm1Hwu/Pten^tm1Hwu; Vhl^tm1Jae/Vhl^tm1Jae; Tg(Cdh16-cre)91Igr/0
• Genetic Background: involves: 129S4/SvJae * BALB/c * C57BL/6J * ICR

• ♀: phenotype observed in females
• ♂: phenotype observed in males
• N: normal phenotype

renal/urinary system

increased kidney cell proliferation ( J:137073 )

• cysts exhibit a 3- to 6-fold increase in the number of Ki-67-positive kidney epithelial cells per mm2 of cortex

kidney cyst ( J:137073 )

• mutants develop multiple epithelial tubule cysts in the kidney cortex and medulla

• cysts develop in all mice (14 of 14) and are seen as early as 6-8 weeks of age

• cysts arise in collecting ducts and distal tubules

• most cysts are lined by a single layer of epithelial cells (simple cysts), whereas ~8% of cysts are lined by multilayered epithelial cells with occasional papillary projections (atypical cysts)

• mutants exhibit reduced frequency of primary cilia in cysts, with distal tubule cysts displaying only ~30% ciliated cells relative to 80-90% ciliated cells in wild-type

kidney cortex cyst ( J:137073 )

• mutants develop multiple epithelial tubule cysts in the kidney cortex

kidney medulla cyst ( J:137073 )

• mutants develop multiple epithelial tubule cysts in the kidney medulla

increased kidney weight ( J:137073 )

• males and females exhibit enlarged and heavier kidneys due to epithelial tubule cysts

abnormal kidney cortex morphology ( J:137073 )

• 3 of 14 mice show isolated regions of benign squamous metaplasia within the kidney cortex

abnormal kidney epithelium morphology ( J:137073 )

• kidney epithelial cells fail to maintain their primary cilia, resulting in uncontrolled proliferation and cyst formation

abnormal renal tubule epithelial cell primary cilium morphology ( J:137073 )

• mutants exhibit reduced frequency of primary cilia in cysts, with distal tubule cysts displaying only ~30% ciliated cells relative to 80-90% ciliated cells in wild-type

abnormal kidney pelvis urothelium morphology ( J:137073 )

• hyperproliferation of the urothelium in the renal pelvis is more pronounced than in single Pten mutants

hydronephrosis ( J:137073 )

cellular

abnormal renal tubule epithelial cell primary cilium morphology ( J:137073 )

• mutants exhibit reduced frequency of primary cilia in cysts, with distal tubule cysts displaying only ~30% ciliated cells relative to 80-90% ciliated cells in wild-type

increased kidney cell proliferation ( J:137073 )

• cysts exhibit a 3- to 6-fold increase in the number of Ki-67-positive kidney epithelial cells per mm2 of cortex

neoplasm

neoplasm ( J:137073 )

N • no tumors areas seen at 3-6 months of age, when mice are euthanized to avoid renal failure

growth/size/body

kidney cyst ( J:137073 )

• mutants develop multiple epithelial tubule cysts in the kidney cortex and medulla

• cysts develop in all mice (14 of 14) and are seen as early as 6-8 weeks of age

• cysts arise in collecting ducts and distal tubules

• most cysts are lined by a single layer of epithelial cells (simple cysts), whereas ~8% of cysts are lined by multilayered epithelial cells with occasional papillary projections (atypical cysts)

• mutants exhibit reduced frequency of primary cilia in cysts, with distal tubule cysts displaying only ~30% ciliated cells relative to 80-90% ciliated cells in wild-type

kidney cortex cyst ( J:137073 )

• mutants develop multiple epithelial tubule cysts in the kidney cortex

kidney medulla cyst ( J:137073 )

• mutants develop multiple epithelial tubule cysts in the kidney medulla

increased kidney weight ( J:137073 )

• males and females exhibit enlarged and heavier kidneys due to epithelial tubule cysts

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
von Hippel-Lindau disease		DOID:14175	OMIM:193300	J:137073